6-35944132-G-T

Variant names:

• chr6-35944132-G-T
• NM_052961.4:c.2681C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052961.4(SLC26A8):​c.2681C>A​(p.Thr894Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T894I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044833302).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.2681C>A	p.Thr894Asn	missense_variant	Exon 20 of 20	ENST00000490799.6	NP_443193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.2681C>A	p.Thr894Asn	missense_variant	Exon 20 of 20	1	NM_052961.4	ENSP00000417638.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.26
DANN	Benign	0.64
DEOGEN2	Benign	0.053	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.42	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.060
Sift	Benign	0.21	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.054	B;B;B
Vest4		0.17
MutPred		0.13		Loss of phosphorylation at T894 (P = 0.0015);.;Loss of phosphorylation at T894 (P = 0.0015);
MVP		0.21
MPC		0.24
ClinPred		0.17	T
GERP RS		0.031
Varity_R		0.13
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35911909;